ASCO 2024 Quality, Equity, and Cost

MCED: Tests May Have a Role in Health Equity, but We’re Not There Yet

If you ask experts about low rates of next-generation sequencing (NGS) and what can be done to improve testing levels to fulfill the promise of precision medicine, it’s a good bet someone will bring up multicancer early detection (MCED), the blood tests that offer the possibility of finding the first cells of cancer in the body.

This is a concept that many like in theory, but the US oncology care system is a long way from offering these tests to patients on a widespread basis, according to panelists of the session, “Multicancer Detection: Is it Ready for Prime Time?” The packed session took place on the first day of the 2024 American Society of Clinical Oncology Annual Meeting.

Jonathan Marron, MD, MPH, FAAP | Image: Dana-Farber/Boston Children’s Hospital

The reality of MCED’s status was borne out when moderator Jonathan Marron, MD, MPH, FAAP, director, clinical ethics in pediatric oncology, Dana-Farber/Boston Children’s Hospital, polled the audience on whether someone had ordered an MCED test for any of their patients in the past year; 75% of the respondents said no.

This is so even though cancer is showing up at earlier ages in young adults, so much so that the US Preventive Services Task Force has lowered the recommended screening age for colorectal cancer¹ and now breast cancer.² These screening methods remain the gold standard and there is no suggestion they should be replaced; MCED would augment existing screening or perhaps provide extra comfort for a person with a significant family history of cancer.

Panelist Robert A. Smith, PhD, senior vice president, American Cancer Society, noted that most tests are in research and development—more than 2 dozen by some estimates.^3,4 He discussed the decision by GRAIL, which developed the Galleri test, to launch the REACH study following the FDA’s approval for the investigational device exemption and CMS’ approval for Medicare coverage of the study.⁵ Panelist Chyke Doubeni, MD, MPH, chief health equity officer, The Ohio State University, noted the Galleri test has achieved breakthrough status⁶ and can test for up to 50 cancers—quite an achievement—but is offered only in settings out of reach of many patients.

A separate study of these tests, called the Vanguard study, is “being driven by” the National Cancer Institute; this is a 3-arm pilot involving 24,000 people.⁷ Other research is underway in the United Kingdom.

Smith noted that the Galleri test is available commercially and often ordered as a laboratory-developed test because it is not covered by insurance. As scenarios the panel outlined showed, what patients want may not matter; what technology can provide and what payers will cover may matter a lot more.

Can MCED Tackle Equity?
MCED has been viewed by some as a way to bring greater equity to genomic testing. But the problem is that the tests are not covered, so for now, the lack of access does not support this argument, some panelists argued.

Audience members weighed in on a scenario involving a Miss Johnson, aged 45 years, and whether an MCED test might help address her interest in keeping regular tabs on her cancer status, as she has Lynch syndrome and several family members have developed Lynch-related cancers. Would MCED help, given her difficulty getting to visits? The room was divided: Half did not want to test due to “incomplete knowledge about risks and benefits,” 30% said it should be Miss Johnson’s preference, and 22% said testing might provide useful information. No one in the audience selected the option regarding cost, but the panelists did.

Jamie Renee Brewer, MD | Image: FDA

Said panelist Jamie Renee Brewer, MD, of the FDA: “If a patient is having trouble with access [and] if a patient is dealing with issues of financial toxicity, the MCED test in itself is probably not going to solve those problems. There’s a cost component associated with the test itself,” she said. And if the test comes back positive, “a patient has to go on what a lot of people are calling a ‘diagnostic odyssey’ to figure out what’s the origin of this particular cancer signal.”

The optimism surrounding the tests, Brewer said, is offset by the need “to be really intentional” about how cost affects access. When designing clinical trials, she said, stakeholders must be “thinking about access and equity there and ensuring that we’re enrolling patients to those trials that represent the US population.”

The cost of MCED testing would be a nonstarter for Doubeni, who is a family physician. “I’ve had the opportunity and privilege of having to discuss these with patients in my clinical practice. The cost is real. And so I do not think I’ll be able to recommend this for this patient just because of the cost,” which would be $1000.

The tests may have a role at some point, “but I do think that equity as an argument for this test may be a stretch,” Doubeni said. “But I don’t want to say that it doesn’t have a role in potentially addressing equity issues.”

What Are the Risks?
Marron noted that MCED cannot be seen as a replacement for certain well-known cancer screens with decades of evidence. Brewer, as a regulator, notes that testing sensitivity varies with the type of test and the prospect of a new testing paradigm raises a host of questions for the clinician. Doubeni worries that the convenience of a blood test could make it easy for busy clinicians to lean on MCED if they lack an understanding of the appropriateness of which test to use in which circumstance.

Other concerns are lack of specificity and the risk of overdiagnosis or false positives, which could increase anxiety and costs, Smith said. Doubeni noted that finding an indolent cancer creates challenges with current screening methods. Brewer said the numbers of potential false positives creates cost concerns that must be considered.

“In some ways, it will come down to patient preferences,” he said.
“One of the things that we’ve observed over the years is that we don’t do a very good job of preparing the clinician for what they should do,” Smith said. Brewer is correct about the need for guidance, he said.

“It’s a little early in the game to answer some of these questions,” Smith said. “But the fact that we’re bringing them up now, I think, is important because we want to be cautious and not just presume that any patient would understand the different circumstances where they might think, ‘Well, maybe I don’t need to keep getting mammograms.’”

References
1. Final recommendation statement: colorectal cancer screening. US Preventive Services Task Force. May 18, 2021. Accessed June 5, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/colorectal-cancer-screening
2. Final recommendation statement: breast cancer screening. US Preventive Services Task Force. April 30, 2024. Accessed June 5, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening
3. Mauracher J. What are multicancer early detection (MCED) tests, and should you get one? MD Anderson Cancer Center. August 25, 2023. Accessed June 5, 2024. https://bit.ly/3KtrZ83
4. Guerra CE, Sharma PV, Castillo BS. Multi-cancer early detection: the new frontier in cancer early detection. Annu Rev Med. 2024;29(75):67-81. doi:10.1146/annurev-med-050522-033624
5. GRAIL to initiate REACH study to evaluate clinical impact of Galleri multi-cancer early detection (MCED) test among the Medicare population. News release. GRAIL. November 20, 2023. Accessed June 5, 2024. https://grail.com/press-releases/grail-to-initiate-reach-study-to-evaluate-clinical-impact-of-galleri-multi-cancer-early-detection-mced-test-among-the-medicare-population/
6. GRAIL announces significant progress with multi-cancer early detection test, including FDA breakthrough device designation. News release. GRAIL. May 13, 2019. June 4, 2024. https://grail.com/press-releases/grail-announces-significant-progress-with-multi-cancer-early-detection-test-including-fda-breakthrough-device-designation/
7. Preliminary Vanguard Study. Division of Cancer Prevention, National Cancer Institute. Accessed June 5, 2024. https://prevention.cancer.gov/major-programs/cancer-screening-research-network-csrn/preliminary-vanguard-study

Costs, Geography Create Barriers to Access for Effective Therapies in Cancer

The high cost of immune checkpoint inhibitors (ICIs) has created potential barriers for patients with lower incomes. Expanding insurance or better targeting patients who could benefit from treatment could help improve access or the cost-effectiveness of these therapies, according to 2 posters presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. Additional posters focused on other ways to improve access to treatments.

Cost-Effectiveness of CDK4/6 Inhibitors in Breast Cancer
Research from authors at Duke Cancer Institute in North Carolina and the University of Virginia in Charlottesville specifically analyzed CDK4/6 inhibitors for patients with hormone receptor (HR)–positive and HER2-negative (HR+/HER2–) metastatic breast cancer.¹ The introduction of these therapies has significantly enhanced survival outcomes for these patients, but there is little evaluation on the cost-effectiveness of these therapies using real-world data.

The researchers used data from Flatiron Health’s deidentified database and Surveillance, Epidemiology, and End Results (SEER) claims data from 2015 to 2021 to assess the cost-effectiveness of CDK4/6 inhibitors plus endocrine therapy (ET) vs ET alone as well as to differentiate between the costs for medication and all other costs for care.

The average (SD) cost of ET was $5158 ($14,460.10), which jumped to $240,785.90 ($204,484.90) for ET plus CDK4/6 inhibitors. Although the medication cost of ET was significantly lower than ET plus CDK4/6, the nonmedication costs of ET were more. For ET, the average nonmedication costs were $66,046.64 ($95,394) compared with $43,611.14 ($48,797.30) for ET plus CDK.

Although the nonmedication costs were significantly lower with the CDK4/6 inhibitors plus ET, the amount saved was only one-tenth the amount of the excess costs for using the combination vs ET alone.

“Lowering CDK4/6 [inhibitor] drug prices or targeting patients who benefit the most could improve cost-effectiveness from a Medicare
perspective,” the authors concluded.

The study was funded by the American Cancer Society and Flatiron Health.

Disparities With the High Cost of ICIs
ICIs are currently available for multiple cancers, including melanoma, HR+/HER2– breast cancer, non–small cell lung cancer (NSCLC), and renal cell carcinoma (RCC); however, the high cost of these therapies has raised concerns that they may increase disparities in cancer survival depending on insurance coverage.

Researchers from the American Cancer Society and Emory University in Atlanta, Georgia, utilized the National Cancer Database to identify patients with newly diagnosed stage IV melanoma (n = 9992), HR+/HER2– female breast cancer (n = 13,632), NSCLC (n = 113,866), and RCC (n = 15,403).²

After the introduction of ICIs, the 2-year survival rate across all cancers increased, but the rates for patients with private health insurance increased more compared with patients who were uninsured.

The study results found 2-year survival increased:

• From 17.5% to 24.4% for melanoma in the uninsured group and from 29.6% to 41.8% for the private insurance group
• From 58.2% to 61.6% for HR+/HER2– breast cancer in the uninsured group and from 74.5% to 78.4% in the private insurance group
• From 11.5% to 15.4% for NSCLC in the uninsured group and from 21.3% to 28.2% in the private insurance group
• From 25.2% to 33.4% for RCC in the uninsured group and from 37.7% to 48.8% in the private insurance group

“The introduction of high-cost immune checkpoint inhibitors was associated with increased disparities in survival by health insurance status for multiple cancers,” the authors concluded. “Policies to expand health insurance coverage and make new treatments more accessible for all are needed.”

Access to Trials for Bispecific Antibodies

Similar to ICIs, bispecific antibodies have shown promising results for diffuse large B-cell lymphoma (DLBCL), with an increase in the number of trials for these therapies. However, there are geographic and racial disparities in access to trials for bispecific antibodies to treat DLBCL, according to one poster.³

The researchers searched ClinicalTrials.gov in May 2023 and included 13 of 51 trials with 1 or more open sites in the US in the systematic review. In addition, information on race and ethnicity was gathered from the 2020 US Census Bureau data.

Overall, 62% of the trials were phase 1, 23% were phase 2, and 15% were phase 1/2, with a total of 885 patients enrolled or expected to enroll in the trials. The majority (69%) were only open in the US. The 50 study sites were distributed in 24 states, but the majority of states (27) had no open trials of bispecific antibodies.

Although California had the highest number of study locations and open studies, Midwestern states had the greatest number of trials (28%) followed by Southern states (26%), Northeastern states (24%), and Western states (22%).

Only 5 states had at least 50% of the African American population living in a county with an open trial. Overall, only 20% of African American individuals lived in a county with a trial. Furthermore, 9 of the 10 states with the highest proportion of African American residents had no trial sites or only 1 trial site.
“There is significant geographic and racial disparity in accessing bispecific antibody trials for DLBCL,” the authors wrote. “Strategies should be framed to address the causes of observed disparities and to improve access to these trials.”

Accessing AlloHCT
Only one-third of patients who need an allogeneic hematopoietic cell transplantation (alloHCT) may receive one, but targeted outreach initiatives could help overcome barriers, according to research from the Center for International Blood and Marrow Transplant Research, a research collaboration between the Medical College of Wisconsin in Milwaukee and the National Marrow Donor Program.⁴

The research included 3141 US counties to examine the associations between social vulnerability, physician density (providers per 10,000 population), and the estimated unmet need for alloHCT (per 100,000 county population). The Social Vulnerability Index (SVI) score ranges from 0 (least vulnerable) to 1 (most vulnerable). The state percentage of unmet need was correlated with SVI (r = 0.494; P < .001) and physician density (r = –0.295; P = .036). The unmet need was validated and calculated using SEER and US Census data.

The researchers considered at-risk counties as those with moderate or high SVI and unmet need for alloHCT as well as a low or very low physician density. Texas had the greatest total population in at-risk counties with approximately 12.2 million people, followed by New York (7.5 million), North Carolina (4.1 million), Florida (3.5 million), and Nevada (3.0 million).

The state-level statistics for the 5 states with the largest population in at-risk counties were as follows:

• The SVI scores were 0.71 for Texas, 0.46 for New York, 0.69 for North Carolina, 0.71 for Florida, and 0.59 for Nevada.
• Physician density was 0.28 for Texas, 0.5 for New York, 0.42 for North Carolina, 0.42 for Florida, and 0.23 for Nevada.
• The estimated percentage of unmet need was 63% for Texas, 51% for New York, 67% for North Carolina, 60% for Florida, and 73% for Nevada.

“Targeted outreach initiatives can be prioritized through a better understanding of how social vulnerability, physician density, and estimated unmet need relate to alloHCT access,” the authors concluded.

References
1. Pilehvari A, You W, Kimmick G, Bonilla G, Anderson R. Unveiling the cost-effectiveness of CDK4/6 inhibitors in treating patients with HR+/HER2- metastatic breast cancer: a closer look at nonmedication expenses. Abstract presented at: American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, IL. Abstract 1532. https://doi.org/10.1200/JCO.2024.42.16_suppl.1532
2. Zhao J, Graetz I, Howard D, Yabroff R, Lipscomb J. Association of high-cost immune checkpoint inhibitor introduction and changes in survival disparities by health insurance coverage among individuals newly diagnosed with advanced cancers in the US. Abstract presented at: American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, IL. Abstract 1580. https://doi.org/10.1200/JCO.2024.42.16_suppl.1580
3. Shahzad M, Khalid MF, Park R, Amin MK, Anwar I, Jaglal MV. Geographic and racial disparities in bispecific antibodies trials access for diffuse large B-cell lymphoma. Abstract presented at: American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, IL. Abstract 1525. https://doi.org/10.1200/JCO.2024.42.16_suppl.1525
4. Watters S, Preussler J, Meyer C, Senneka M. Identifying states for targeted alloHCT access initiatives using social vulnerability, physician density, and unmet need. Abstract presented at: American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, IL. Abstract 1528. https://doi.org/10.1200/JCO.2024.42.16_suppl.1528

Posters Showcase Positive Data on Denosumab, Pegfilgrastim Biosimilars

Posters from the American Society of Clinical Oncology 2024 Annual Meeting demonstrate positive safety and efficacy data for denosumab and pegfilgrastim biosimilars.

Denosumab Biosimilar Data in Postmenopausal Osteoporosis
Findings from one study supported the therapeutic equivalence and similar safety profiles of a denosumab biosimilar candidate (FKS518) compared with the originator (Prolia/Xgeva) in postmenopausal women with osteoporosis.¹

FKS518, a candidate biosimilar of denosumab (a RANKL inhibitor used for bone metastases and multiple myeloma), was studied to establish biosimilarity through the LUMIADE-3 trial (NCT04934072).

The study included 553 women aged 55 to 85 years randomly assigned to receive either FKS518 (n = 276) or the denosumab originator (n = 277). The primary efficacy end point was the percentage change in lumbar spine bone mineral density (LS-BMD) at week 52. Patients were administered three 60-mg doses, with those on the originator product being randomly reassigned at week 52 to continue their treatment or switch to the biosimilar.

Results showed significant increases in LS-BMD in both the FKS518 and originator groups. The lower bound of the 90% CI for noninferiority (–0.05) was above –1.45, and the upper bound for nonsuperiority (1.20) was below
1.45, confirming therapeutic equivalence. Secondary end points, including changes in bone mineral density at the femoral neck and total hip, also demonstrated similar percent changes from baseline in both groups.

Safety evaluation indicated no notable differences between FKS518 and the
originator, with treatment-emergent adverse events occurring in 67.6% of patients: 66.8% in the FKS518 group and 68.5% in the originator group.

Pegfilgrastim Biosimilar in Patients Receiving Cytotoxic Chemotherapy
Findings from a second study found that biosimilar pegfilgrastim was safe and effective in patients with various cancer types receiving cytotoxic chemotherapy.²

Despite pegfilgrastim being essential for preventing chemotherapy-induced neutropenia and newer biosimilars emerging as promising alternatives with trials showing comparable efficacy, conclusive clinical benefit evidence is lacking, likely due to low statistical power in these trials.

A systematic review and meta-analysis were conducted, analyzing data from 10 randomized controlled trials published before October 2023 featuring 2237 patients being treated with cytotoxic chemotherapy to compare the efficacy and safety of conventional pegfilgrastim and its biosimilars.

Studies included had to report at least 1 primary outcome: duration of severe neutropenia (DSN) after the first chemotherapy cycle, incidence of febrile neutropenia (FN), or bone pain. The analysis calculated pooled risk ratios (RRs) and weighted mean differences (WMDs).

Biosimilars showed a significant reduction in DSN (WMD = –0.08 days; 95% CI, –0.15 to –0.01; P = .03). There were no significant differences in FN incidence (RR, 0.98; 95% CI, 0.62-1.53) or bone pain (RR, 0.98; 95% CI, 0.82-1.17).

Additionally, eflapegrastim, another long-acting granulocyte-colony stimulating factor agent, significantly reduced DSN compared with conventional pegfilgrastim (WMD, n = –0.13 days; 95% CI, –0.24 to –0.03; P = .01). The researchers recommended “exploring the impact of the drug in clinical settings on costs and patient-reported outcomes could provide valuable insights into optimizing the management of chemotherapy-related neutropenia.”

References
1. Sadek J, Valter I, de Souza A, Szeles P, Monnet J. A randomized, double-blind study to evaluate the efficacy, pharmacodynamics, safety and immunogenicity of FKS518, a proposed denosumab, with the originator in postmenopausal women with osteoporosis (LUMIADE-3 study). Abstract presented at: American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, IL. Abstract 3155.
2. Nasir S, Ali I, Salim SS, Alidina Z, Idrees H, Moosajee M. Comparative efficacy and safety profiles between conventional pegfilgrastim and its biosimilar agents in patients receiving cytotoxic chemotherapy: a systemic review and meta-analysis. Abstract presented at: American Society of Clinical Oncology; May 31-June 4, 2024; Chicago, IL. Abstract 12115.

Further Medicaid Expansion Would Benefit Patients With Melanoma, Study Finds

At the 2024 American Society of Clinical Oncology Annual Meeting, a poster presentation demonstrated the value of Affordable Care Act Medicaid expansion for patients with melanoma. In the investigators’ assessment, expanding this coverage improved patient outcomes by facilitating early-stage diagnoses.¹

When health care coverage is extended to individuals from low-income households or communities, it can go a long way toward reducing health disparities. These disparities largely impact people of color, Medicaid.gov reported, stating that over 25% of the uninsured adults who would qualify for expanded Medicaid are people of color.² Expanding available coverage, which has not been achieved in every state, could directly impact these communities, they add. For example, prostate cancer affects Black men at a higher rate than White men. Should Medicaid coverage become more widely available, there is an increased chance for early treatment interventions and diagnosis to improve patient outcomes.

Although these data suggest the influence Medicaid expansion could have across the spectrum of health care, Win et al’s presentation titled, “The positive impact of Medicaid expansion on melanoma stage at presentation,” detailed how the policy could affect outcomes in melanoma.¹

The researchers utilized The National Cancer Database to identify 12,667 individuals with a new melanoma diagnosis who had Medicaid coverage. Other patients with melanoma were excluded if they had Medicare, private insurance, or an additional form of known or unknown insurance. The analysis spanned the pre-expansion period of 2010 to 2013 and the postexpansion period of 2014 to 2020. Annual trends and difference-in-difference (DID) assessments were performed to investigate tumor staging throughout states that have expanded Medicaid coverage (MES) and those that have not (non-MES).
The study population was 56% male and 95% White. Additionally, 59% of patients had Medicaid coverage between 2010 and 2020. The remaining 41% were uninsured during that time. Notably, the researchers saw uninsured rates significantly drop from 51% in 2010 to 16% by 2020.

In total, 21% of included patients were diagnosed with stage III melanoma and 18% with stage IV. In MES, the rate of stage IV melanoma at presentation fell from 21% to 17% by the end of the 10-year study period. Contrarily, in non-MES, these rates increased from 20% to 23% in the same period. After DID analysis was performed to evaluate the pre- and postexpansion periods, the researchers saw statistically significant decreases in both 3-year mortality (DID, –0.05; P < .001) and stage IV melanoma at presentation (DID, –0.04; P < .001). Furthermore, the researchers noted that immunotherapy was administered in cases of stage IV melanoma at a significantly higher rate in MES vs non-MES (47% vs 41%; P < .001).

In their conclusion, the authors emphasized the capacity for expanded Medicaid and health care services to lead to early-stage diagnosis in melanoma and reduced mortality rates. Their analysis still revealed, however, that as of 2020, 16% of patients remained uninsured. With this reality in mind, they advocated for dedicating increased efforts to providing quality care to the uninsured to improve outcomes in this population.

In 2024, an estimated 7.7% people in the US—approximately 26 million—remain uninsured.³

References
1. Win S, Amini A, Modi B, et al. The positive impact of Medicaid expansion on melanoma stage at presentation. J Clin Oncol. 2024;42(suppl 16). Abstract 1533. doi:10.1200/JCO.2024.42.16_suppl.1533
2. Medicaid expansion helps address health disparities. Medicaid. Accessed June 19, 2024. https://www.medicaid.gov/about-us/program-history/medicaid-50th-anniversary/entry/47671
3. Minemyer P. CDC: uninsured rate fell by 26% between 2019 and 2023. Fierce Healthcare. June 18, 2024. Accessed June 19, 2024. https://www.fiercehealthcare.com/payers/cdc-uninsured-rate-fell-26-between-2019-and-2023

SPOTLIGHT: Clinical Trials Won’t Cause Financial Harm for Practices in
Medicare Payment Models, Study Finds

Multiple barriers can prevent patients with cancer from enrolling in clinical trials. One can be the concern that putting a patient on study costs more money; if a physician-owned practice is taking part in an alternative payment model (APM), there may be a fear among those making the decision to refer patients to clinical trials that doing so will undermine a model’s savings targets.

To examine these concerns, investigators with Sarah Cannon Research Institute (SCRI) Oncology Partners and The US Oncology Network used data developed during the years of the Oncology Care Model (OCM) to study the effects of trial participation on hospitalization, drug spending, hospice stays, and overall costs within the context of the OCM, CMS’ model for Medicare patients with cancer than ran from July 2016 through June 2022.¹

Ishwaria Subbiah, MD | Image: SCRI Oncology Partners

In 2 abstracts presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, investigators led by Ishwaria Subbiah, MD, executive director of Supportive Care Oncology, Health Equity and Professional Well-being at SCRI Oncology Partners presented results based on data from 121,171 patients with cancer who were treated in practices across The US Oncology Network under the OCM from July 1, 2017, to June 30, 2022.^2,3 Data came from 323 practice sites in 11 states.

Findings in both abstracts are described by “episodes,” which were the 6-month periods of care the OCM used to measure spending and quality. The episode framework is retained under the Enhancing Oncology Model (EOM), the successor APM that launched July 1, 2023, and was scheduled to reopen for new applicants July 1, 2024, with key reimbursement changes.⁴
Across the 2 abstracts that SCRI Oncology Partners and The US Oncology Network presented at ASCO, investigators found the following:

Over 5 years, spending for Medicare beneficiaries with cancer in clinical trials was higher than usual care by $2341 per episode (P < .0001); however, savings when measured against OCM benchmarks were significantly greater among patients in clinical trials than for usual care patients, $4816 vs $826, respectively (P < .0001).²

Hospital use was greater among patients on clinical trials,2 but observation visits and trips to the emergency department (ED) were no different among patients receiving usual care.2 Drug expenditures were about the same for both groups.³

Patients on trials were no less likely to enroll in hospice less than 3 days before death, compared with those in usual care (56.8% vs 52.6%), and duration of days on hospice for trials (8 days) vs usual care (9 days). Neither difference was significant.³

For insights on the findings, Evidence-Based Oncology (EBO) spoke with Subbiah during an interview at ASCO. This interview is lightly edited for length and clarity.

EBO: Can you discuss the value of having such a large data set for this research?

Subbiah: It was very important that we have the full picture, that we
not look only at any individual slice of data. For this particular initiative, we looked at our OCM data, or practices that were participating in model. The denominator was that every person who had [participated in the OCM] would fall under that model. So by virtue of being something driven by CMS, we were able to capture a critically important and vulnerable population, which is the older adults aged 65 years and above, their experience with cancer and their cancer journey, and how clinical trial participation factored in with other important anchoring elements of the cancer journey. That’s really what brought these particular projects together. We have such a complete, robust view of an older adult’s journey. Let’s understand what’s happening in a data-driven way.

EBO: It’s a very, very big group.

Subbiah: It’s a big group that allowed us to not be as preoccupied with any outliers.

EBO: When it comes to considering a referral to a clinical trial, is there a perception from some community oncologists: What’s going to happen if I add all these costs to my practice? Is that something physicians worry about?

Subbiah: The practices are all independent, so for those who are leading those practices, there’s a level of investment in the health and well-being of the practice as much as it is about taking care of patients and taking great care of their people. So in that way, the work that we do on my team does center on how we can be facilitators to bring clinical trials into the community.

We focus heavily on the administrative burden of clinical trials. We ask: What does it take for the well-intentioned practice to be able to offer studies? Looking at that administrative burden on practices is a very [important] area of work because we know that in order to have that research infrastructure, it requires a substantial investment.

How does offering trials actually impact the elements of care that we think it impacts? It was important to quantify the costs of care; it’s just 1 element where you can take out that perception, put in the data, and then put in the reality. Across both areas of the work from this data set that we presented at ASCO, that’s one of the common threads: 1 abstract was about cost—and getting clarity on the cost of care—and the second project was about perceptions of end-of-life care and the quality of end-of-life care by comparing those who would have participated in a trial vs usual care. So allow us to take out that perception pin and put in the actual data.

EBO: You’ve started with OCM data, because that’s the model The US Oncology Network practices were in for so many years. Now that CMS is going to reopen the EOM, increase the financial incentives, and favorably change 1 risk factor, it could affect whether practices decide to give the EOM another look.4 What can we assume about clinical trials in the EOM based on these findings? Is there applicability of these findings for practices considering the EOM?

Subbiah: I think these findings add another element of “What does the EOM experience mean—implementing it in the real world?” In that way, you have evidence on how the EOM interfaces with a clinical trial being offered in the clinic, and then the patient’s participation in the trial. And that’s an element of real-world cancer care that needed clarity. For APMs, how will they behave in common, real-world care settings? We’re hard-pressed to find an oncology guideline that doesn’t have “consider clinical trial participation” right up there.

Part of these efforts is to make sure that those reading this work and those who work in clinical oncology are thinking about clinical trial participation with the same mindset they have when they are looking at possibly participating in alternative payment models because it shouldn’t be a silo. When you look at it from the patient side, it’s a person, their family, their caregivers, and it’s 1 journey for them. So part of this is taking the holistic view of the patient’s experience and having these dimensions of evidence to help understand the true impact of EOM and [ensuring that] innovation of care delivery, especially in the real-world setting, involves data-driven equity.

EBO: Results for emergency department readmissions always get attention because that has been such a priority for CMS. Can you discuss those findings?

Subbiah: If you call being a trial participant aggressive treatment, that is a perception in and of itself. Except when you pause and reflect on the standard of care alternatives, in the second- and third-line setting, [treatment] may be profoundly toxic compared to the trial. The trial option may actually be toxic, but there’s also the importance of quantifying health care utilization, especially unplanned health care utilization in the context of the different care settings. And so, in that way, what we want to be able to show is this kind of this interplay. Does trial participation actually result in more ED visits? And more importantly, what happens after the ED visits?

This is a population with advanced cancer, and when you’re thinking about unplanned health care utilization, as payers and as regulatory entities, you think of it in the context of end-of-life care or aggressiveness of care toward the end of one’s life. So it was important for us to be able to demonstrate that the answers don’t begin and end with the ED visit; it may be that that touch point with a doctor is what was needed to get plugged in with home hospice or palliative care or other elements of essential care. And in doing so, we were able to show through these findings that hospice utilization and duration of time spent on hospice was no different.

You’re directly countering a perception that trial participation, which is thought of as aggressive, is associated with inferior end-of-life outcomes. The evidence simply doesn’t back that up. In broadening access to clinical trials—getting older adults to be represented on the clinical trials and, frankly, getting all communities represented on trials—we’re going to have to tackle each of the perceptions with evidence. In each case, let’s take a perception and replace it with the evidence from our own backyard. That way, you’re not having to extrapolate findings from a care setting that doesn’t resemble your clinic in any way.

EBO: That’s another benefit of your data set: Not only is it large, but it’s data from the practices that you are working with. Would these findings, then, be more believable?

Subbiah: Exactly. The data are from across multiple practices, parent practices, and multiple locations from 323 clinic locations. By having that footprint, you’re mitigating any biases from just focusing on a single clinic or cancer center. And the data are from across different states as well.

EBO: Now that you have these results, where do you go from here?

Subbiah: As we learn lessons from our own experience, we share that as pearls of wisdom, not a 30-page manifest. You’re talking about clinics with multidisciplinary, expert practitioners in different roles. You want the key points to land as quickly as possible so that the perception is taken out and the data are put back in. And that’s all part of that overarching effort to have broader representation of older adults on clinical trials. It’s about unpacking individual barriers. These individual barriers aren’t just experienced by 1 or 2 people. It is felt across a much broader portion of the population, but these are never barriers that would get a platform on their own. Both within The US Oncology Network and the partnership with Sarah Cannon Research Institute, it’s taking evidence like this that’s generated in the community setting and making the case for streamlining certain elements of study design and implementation. It’s chipping away at the behemoth that is the clinical trial.

References
1. Caffrey M. Amid concerns, will practices take part in the Enhancing Oncology Model? Am J Manag Care. 2023;29(spec no. 4):SP328.
2. Subbiah IM, Indurlal P, Alam N, et al. 5-year multicenter analysis of clinical trial participation and total cost of care for older adults with cancer. J Clin Oncol. 2024;42(suppl 16). Abstract 11013. doi:10.1200/JCO.2024.42.16_suppl.11013
3. Subbiah IM, Indurlal P, Deepak D, et al. Clinical trial participation and end-of-life care among older adults: a multi-center longitudinal observational cohort analysis of 121,717 patients with cancer. J Clin Oncol. 2024;42(suppl 16). Abstract 11181. doi:10.1200/JCO.2024.42.16_suppl.11181
4. Caffrey M. CMS reopens EOM with payment boost, extends model to 2030. AJMC. May 30, 2024. Accessed June 15, 2024. https://www.ajmc.com/view/cms-reopens-eom-with-payment-boost-
extends-model-to-2030